A5015003745- Hereditary Neurological Disorders
- Lipid metabolism and disorders
- RNA Research and Splicing
- Virus-based gene therapy research
- Peroxisome Proliferator-Activated Receptors
- Nuclear Structure and Function
- Caveolin-1 and cellular processes
- Toxin Mechanisms and Immunotoxins
- Neurological diseases and metabolism
- Ion channel regulation and function
- Renal and related cancers
- Metabolism and Genetic Disorders
- Neurofibromatosis and Schwannoma Cases
- RNA and protein synthesis mechanisms
- Skin and Cellular Biology Research
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- CRISPR and Genetic Engineering
- Sarcoma Diagnosis and Treatment
- Genomics and Rare Diseases
- Renal Diseases and Glomerulopathies
- Ion Transport and Channel Regulation
- Prenatal Screening and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Cellular Mechanics and Interactions
Southmead Hospital
2015-2024
North Bristol NHS Trust
2015-2024
University of Bristol
2023
Genomics England
2023
University Hospitals Bristol and Weston NHS Foundation Trust
2023
University Hospitals Bristol NHS Foundation Trust
2023
Illawarra Health and Medical Research Institute
2022
University of Wollongong
2022
Bristol Royal Hospital for Children
2017
Bristol Robotics Laboratory
2017
BackgroundFetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; detectable microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy CNVs is routine during the investigation fetal but there little information on clinical usefulness genome-wide next-generation sequencing prenatal setting. We therefore aimed to evaluate proportion fetuses with...
Inherited peripheral neuropathy (IPN) is a clinically and genetically heterogeneous group of disorders with more than 90 genes associated the different subtypes. Sequential gene screening gradually being replaced by next generation sequencing (NGS) applications. We designed validated targeted NGS panel assay including 56 known causes IPN. report our findings following testing 448 patients types clinically-suspected Genetic diagnosis was achieved in 137 (31 %) involved 195 pathogenic variants...
Activation of the cellular DNA damage response is detrimental to adenovirus (Ad) infection. Ad has therefore evolved a number strategies inhibit ATM- and ATR-dependent signaling pathways during Recent work suggests that Ad5 E4orf3 protein prevents ATR activation through its ability mislocalize MRN complex. Here we provide evidence indicate Ad12 different strategy from ATR. We show utilizes CUL2/RBX1/elongin C-containing ubiquitin ligase promote proteasomal degradation activator...
ABSTRACT Adenovirus type 5 (Ad5) inactivates the host cell DNA damage response by facilitating degradation of Mre11, ligase IV, and p53. In case p53, this is achieved through polyubiquitylation Ad5E1B55K Ad5E4orf6, which recruit a Cul5-based E3 ubiquitin ligase. Recent evidence indicates that paradigm does not apply to other adenovirus serotypes, since Ad12, but Ad5, causes TOPBP1 action E4orf6 alone Cul2-based We now have extended these studies groups A E. While infection Ad4, Ad12 (groups...
Background and aimsPrognosis management differ between familial chylomicronaemia syndrome (FCS), a rare autosomal recessive disorder, multifactorial (MCS) or severe mixed hyperlipidaemia. A clinical scoring tool to differentiate these conditions has been devised but not validated in other populations. The objective of this study was validate score the UK population identify any additional factors that might improve it.MethodsA retrospective validation conducted using data from 151 patients...
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder. This study aimed to the genotype distribution of FCS-causing genes in United Kingdom, genotype-phenotype correlation, and clinical differences between FCS multifactorial (MCS). METHODS: The included 154 patients (FCS, 74; MCS, 80) from UK national registry arm International Quality Improvement Service Evaluation Project. RESULTS: was relatively common non-Europeans those with parental consanguinity (...
Malignant peripheral nerve sheath tumours (MPNSTs) are a major cause of mortality in patients with neurofibromatosis 1 (NF1). We have analysed lymphocyte DNA samples from 30 NF1 MPNSTs to determine their underlying constitutional gene mutations. Mutations were detected 27/30 (90%) these patients. mutations identified included nonsense, missense, frameshift, splice site mutation and single or multi-exonic deletions no obvious clustering the across gene. Fourteen represent novel changes. There...
ABSTRACT The ability of adenovirus early region proteins, E1B-55K and E4orf6, to usurp control cellular ubiquitin ligases target proteins for proteasome-dependent degradation during infection is well established. Here we show that the E4 gene product, E4orf3 can, independently transcriptional corepressor intermediary factor 1γ (TIF1γ) proteasome-mediated infection. Initial mass spectrometric studies identified TIF1 family members—TIF1α, TIF1β, TIF1γ—as E1B-55K-binding in both transformed...
Abstract Background Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be significant onset SRNS. We report cases the UK and demonstrate vivo functional effects Nup93 depletion fly ( Drosophila melanogaster) nephrocyte model. Methods Three hundred thirty-seven SRNS patients from National cohort with Nephrotic Syndrome (NephroS) were...
Pathogenic variants in the Glycyl-tRNA synthetase gene cause allelic disorders Charcot-Marie-Tooth disease type 2D and distal hereditary motor neuropathy V. We describe clinical features 8 unrelated patients found to have by Next Generation Sequencing. In addition upper limb predominant symptoms, other presentations included failure thrive, feeding difficulties lower dominant symptoms. Variability age at testing ranged from 14 months 59 years. The youngest being symptomatic 3...
Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a birth incidence of 1/3,500. Around 50% cases are due to new mutations. The NF1 gene maps 17q11.2 and encodes neurofibromin. “classical” tumor suppressor gene. Congenital disseminated rare just two previously reported. We present deceased baby congenital in whom we performed molecular studies. A germline mutation (R461X) exon 10a the was found. 2 bp deletion (3508delCA) codon 1170 21 identified DNA derived from...